Iron status in early life and associations with developmental outcomes

Infants and young children are at particular risk of iron deficiency and its associated consequences for growth and development. The main objectives of this thesis were to quantify iron intakes, status and determinants of status in two year olds; explore determinants of neonatal iron stores; investigate associations between iron status at birth and two years with neurodevelopmental outcomes at two years and explore the influence of growth on iron status in early childhood, using data from the Cork BASELINE (Babies after SCOPE: Evaluating Longitudinal Impact using Neurological and Nutritional Endpoints) Birth Cohort Study (n=2137). Participants were followed prospectively with interviewer-led questionnaires and clinical assessments at day 2 and at 2, 6, 12 and 24 months. At two years, there was a low prevalence of iron deficiency and iron deficiency anaemia in this cohort, representing the largest study of iron status in toddlers in Europe, to date. The increased consumption of iron-fortified products and compliance with recommendations to limit unmodified cows’ milk intakes in toddlers has contributed to the observed improvements in status. Low serum ferritin concentrations at birth, which reflect neonatal iron stores, were shown to track through to two years of age; delivery by Caesarean section, being born small-for-gestational age and maternal obesity and smoking in pregnancy were all associated with significantly lower neonatal iron stores. Despite a low prevalence of iron deficiency in this cohort, both a mean corpuscular volume <74fl and ferritin concentrations <20μg/l were associated with lower neurodevelopmental outcomes at two years. An inverse association between growth in the second year of life and iron status at two years was also observed. This thesis has presented data from one of the largest, extensively-characterised cohorts of young children, to date, to explore iron and its associations with growth and development.

Pleiotropic Analysis of Lung Cancer and Blood Triglycerides

Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.1 (rs6904596, ZNF184) was associated with both lung cancer (P = 5.50x10(-6)) and blood triglycerides (P = 1.39x10(-5)). We replicated the association in 6097 lung cancer case patients and 204 657 control subjects (P = 2.40 × 10(-4)) and in 71 113 subjects with triglycerides data (P = .01). rs6904596 reached genome-wide significance in lung cancer meta-analysis (odds ratio = 1.15, 95% confidence interval = 1.10 to 1.21 ,: Pcombined = 5.20x10(-9)). The large sample size provided by the lipid GWAS data and the shared genetic risk factors between the two traits contributed to the uncovering of a hitherto unidentified genetic locus for lung cancer.

Alcohol-Related Problems in Eastern Europe : A Comparative Perspective

This thesis investigates the association between alcohol consumption and alcohol-related harm in Eastern Europe. The main aim was to estimate to what extent changes in per capita alcohol consumption have an impact on different forms of alcohol-related mortality, and to put the results in an international comparative perspective. The thesis includes four papers; the first two papers use aggregate time-series analysis to assess how changes in per capita consumption affect rates in suicide mortality and fatal non-intentional injuries in several Eastern European countries, respectively. The third paper applies the same methodological approach to analyse the population-level relationship between alcohol and homicide in Russia and the U.S.. The fourth paper employs survey data to assess how the risk of experiencing alcohol-related problems in relation to volume of consumption in the Baltic countries compares to Sweden and Italy. The results of the first three papers suggests: (i) that changes in per capita consumption are significantly related to changes in mortality rates of suicide, non-intentional injuries and homicide in the countries under study; (ii) that the relationship is stronger for men than for women, and (iii) that the relationship tends to be stronger in the countries with more detrimental drinking patterns, e.g. Russia. The results of the fourth paper suggest that the risk of experiencing alcohol-related problems in relation to level of drinking in the Baltic countries is similar to the corresponding risk in Sweden, but considerably stronger than in Italy. In conclusion, the findings support the significance of a public health approach to alcohol-related problems in Eastern Europe, i.e., policy measures directed towards total alcohol consumption. In addition, strategies aimed at reducing the occurrence of binge drinking seem to have great potential for reducing alcohol-related harm and mortality in Eastern European countries.

The Health Behaviours in School Children (HBSC) survey 2014

The Health Behaviours in School Children (HBSC) survey 2014 shows that overall health levels are good. There are encouraging findings on consumption of fruit and vegetables, teeth cleaning, and a drop in smoking levels and consumption of sweets and soft drinks.  However, many children said they find it easy to get cigarettes, too many children are going to bed hungry, and there are concerns about levels of cyber bullying. A total of 13,611 pupils were surveyed with questions on topics like general health, food and dietary behaviour, exercise and physical activity, self-care, smoking, use of alcohol and other substances, bullying including cyber bullying, and sexual health behaviours.

Antioxidant and detoxify genes polymorphisms in colorectal cancer predisposition

Colorectal cancer (CRC) results from histologic and gene alterations can lead to a massive cellular proliferation. Most of the authors assume multifactorial causes to CRC genesis. Low physical activity, a fat diet poor in fibers and smoking habits seems to have an important role in CRC. However, there are also genetic causes associated with CRC risk. It has been described that oxidative stress levels could influence CRC development. Thus, cellular balance reactive species and defense enzymes involved in oxidative stress are crucial to maintain a good tissue function and avoid neoplasic process. Therefore, genome variations on these defense enzymes, such as MNSOD, SOD3, GSTP1, GSTT1 and GSTM1, could be important biomarkers to colorectal adenocarcinomas. We intend to determine frequencies distribution of most common polymorphisms involved on oxidative stress regulation (MNSOD, SOD3, GSTP1, GSTT1 and GSTM1) in patients with sporadic colorectal adenocarcinoma (SCA) and in healthy controls, evaluation their possible correlation with SCA risk. Samples common polymorphisms of antioxidant and detoxify genes (MNSOD T175C, SOD3 R213G, GSTP1 A105G, GSTP1 C114T, GSTT1del and GSTM1del) analysis was done by PCR-SSP techniques. In this study we found a higher prevalence of MNSOD 175CC (55% vs 2%; p<0.0001; OR: 58.5; CI 13.3 to 256.7), SOD3 213GG (31% vs 2%; p<0.0001; OR: 21.89; CI 4.93 to 97.29), GSTP1 105GG (46% vs 12%; p<0.0001; OR: 6.14; CI 2.85 to 13.26), GSTP1 114TT (38% vs 0%; p<0.0001; OR: Infinity) and GSTT1 null (75% vs 28%; p<0.0001; OR: 7.71; CI 3.83 to 15.56) mutated genotypes among SCA patients, while the normal genotypes were associated with SCA absence. Furthermore, we found GSTP1 114TT mutated genotype (52% vs 27%; p=0.003; OR: 2.88; CI: 1.41 to 5.89) and GSTT1 null genotype (87% vs 65%; p=0.003; OR: 3.66; CI 1.51 to 8.84) associated with colon samples. These findings suggest a positive association between most of common polymorphisms involved on oxidative stress regulation and SCA prevalence. Dysregulation of MNSOD, SOD3, GSTP1, GSTT1 and GSTM1 genes could be associated with an increase of ROS in colon and rectum tissue and p53 pathway deregulation, induced by oxidative stress on colonic and rectal cells. The present study also provides preliminary evidence that MNSOD 175C, SOD3 213G, GSTP1 105G, GSTP1 114T and GSTT1 null polymorphisms, may be involved in SCA risk and could be useful to clarify this multifactorial disorder.

FATORES DE RISCO PARA DOENÇAS CRÔNICAS NÃO TRANSMISSÍVEIS E VARIÁVEIS SOCIODEMOGRÁFICAS DE SERVIDORES PÚBLICOS

Objetivo: Associar fatores de risco para doenças crônicas não transmissíveis (DCNT) com variáveis sociodemográficas de servidores de uma instituição pública de ensino superior. Métodos: Estudo transversal, realizado no período de 2012 a 2013. Utilizou-se um questionário com variáveis sociodemográficas, fatores de risco para DCNT e aferição de peso e estatura. Classificou-se o estado nutricional de acordo com o índice de massa corporal. Analisaram-se os dados pelos programas Epi-Info 3.2.1 e Bioestat 5.0. As associações foram verificadas pelos testes qui-quadrado de Yates, de tendência e exato de Fisher (p≤0,05). Resultados: Participaram 225 servidores, maioria de mulheres (64,4%), na faixa etária entre 45-54 anos (37,3%) e escolaridade superior a 12 anos de estudo (85,8%). O sexo associou-se ao excesso de peso (p=0,034), consumo diário de leite integral (p=0,023), consumo insuficiente de frutas, legumes e verduras - FLV (p=0,020) e consumo insuficiente de feijão (p=0,000), sendo mais frequentes entre mulheres. Entre os homens, foi mais frequente o consumo excessivo de bebida alcoólica (p=0,000). O excesso de peso associou-se à faixa etária (p=0,008). O hábito de fumar (p=0,004) e o consumo diário de leite integral (p=0,016) apresentaram associação com a escolaridade. Conclusão: Encontrou-se elevada prevalência de fatores de risco para doenças crônicas não transmissíveis na amostra estudada, com associação para sexo, faixa etária e escolaridade. O excesso de peso apresentou maior ocorrência nas mulheres e nas idades acima de 45 anos, hábitos alimentares inadequados no sexo feminino, maior ingestão de bebida alcoólica no masculino e hábito de fumar nos indivíduos com maior escolaridade.

DEVELOPMENT AND REPRODUCIBILITY OF THE INSTRUMENTO DE AVALIAÇÃO DA PROMOÇÃO DA SAÚDE NA UNIVERSIDADE - IAPSU (ASSESSMENT TOOL FOR HEALTH PROMOTION AT THE UNIVERSITY)

Objective: To present the Instrumento de Avaliação da Promoção da Saúde na Universidade – IAPSU (Assessment Tool for Health Promotion at the University) and its reproducibility assessment process. Methods: Cross-sectional study conducted between May and July 2014 with 50 students from a university of Fortaleza, Ceará, which developed the IAPSU through the analysis of government documents and a systematic review of the literature on a potentially healthy university. The tool has 41 questions divided into five domains: physical activity, diet, environmental factors, psychosocial factors and alcohol and drug use, integrative and complementary practices. To assess the inter-examiner reproducibility, the students answered the IAPSU twice, applied by two different examiners; to assess the intraexaminer reproducibility, another application of the instrument was performed after seven days. Results: The study comprised 40 Nursing students and 10 Physical Therapy students, with a mean age of 25 ± 5.4 years; 88% were women and white individuals were predominant. In the reproducibility assessment, strong intraclass, intra- and inter-examiner correlation coefficients - above 0.8 - were observed in all the domains. Conclusion: The IAPSU is a reproducible and reliable instrument for assessing health promotion at the university.

Substance Use and Academic Outcomes among High School Seniors: Examining the Influence of Emotional Academic Engagement

Substance use is prevalent among adolescents, with two-thirds trying alcohol and half trying an illicit drug by twelfth grade (Miech et al., 2015). Substance use is known to affect academic performance. This study utilized nationally representative data from the 2013 Monitoring the Future twelfth grade survey to examine the relationships between substance use, skipping school, grades, and academic engagement. One-quarter of respondents (26%) had never used a substance. The majority (67%) had used at least one substance during the past year. Substance use during their lifetime but not during the past year was uncommon (7%). Lifetime non-users were less likely than past-year users to skip school during the past month and to have low grades. Lifetime non-users also had greater academic self-efficacy and emotional academic engagement relative to past-year users. These findings underscore the importance of screening and intervention for substance use to promote academic achievement and adolescent wellbeing.

A survey on diversity and distribution of crabs in inter tidal and sub tidal shore of the Sistan and Baloochestan Province (Oman sea)

This project was done for identifying and survey on distribution and diversity of true crabs in inter tidal and sub tidal zones of the Gulf of Oman (Sistan and Baluchistan province) during two year from 2009 to 2010. Specimens of inter tidal zones were carried out at 10 stations and 8 stations from sub tidal. The specimens were collected by hand and dip-net from inter tidal and by trawl net from sub tidal regions, preserved in 70% alcohol and carried to the laboratory. A total of 37 species belonged to 17 families from inter tidal and 23 species belonged to 9 families from sub tidal were identified. Of which 54 species were identified up to species level. 2 species from Matutidae, 1 species from Eriphiidae, Menippidae, Pseudoziidae, Plagusidae, Varunidae, Camptandriidae, Dromiidae and Dorippidae, 2 species from Oziidae, 3 species from Epialtidae, 2 species from Majidae, 4 species from Pilumnidae, 12 species from Portunidae, 6 species from Xanthidae, 2 species from Grapsidae, 3 species from Dotillidae, 3 species from Macrophthalmidae, 3 species from Ocypodidae, 3 species from Calappidae, 2 species from Parthenopidae and 1 species from Galenidae were identified. All specimens are deposited in the Zoological Museum, University of Tehran (ZUTC). The results of the present study revealed that family Portunidae with 6 species from inter tidal and 9 species from sub tidal regions have the highest species richness among the 22 families. Maximum similarity (Sorenson's Index) was obtained among the stations Breis, Lipar, Pozm and Gordim, and minimum was obtained among the stations Chazire-Kharchang with Pasabandar, Beris, Lipar, Daria-Bozorg, Pozm and Gordim in intertidal regions. In sub tidal regions maximum similarity (Sorenson's Index) was obtained among the stations Pasa bandar with Berisand minimum was obtained among the stations Govatr with Ramin and Gordim, Ramin with Pozm. Also maximum species richness was observed at Tiss in inter tidal and Chabahar in sub tidal stations, whereas minimum was obtained at Beris, Pozm, Gordim and Lipar in inter tidal and Govatr and Pozm in sub tidal stations. Family Ocypodidae in inter tidal and Portunidae in sub tidal regions have the highest distribution. In all of the species length and Breadth of carapace showed significant relation.

Oxidative stress and its haemodynamic consequences in chronic kidney disease

Chronic kidney disease (CKD) is associated with increased cardiovascular risk in comparison with the general population. This can be observed even in the early stages of CKD, and rises in proportion to the degree of renal impairment. Not only is cardiovascular disease (CVD) more prevalent in CKD, but its nature differs too, with an excess of morbidity and mortality associated with congestive cardiac failure, arrhythmia and sudden death, as well as the accelerated atherosclerosis which is also observed. Conventional cardiovascular risk factors such as hypertension, dyslipidaemia, obesity, glycaemia and smoking, are highly prevalent amongst patients with CKD, although in many of these examples the interaction between risk factor and disease differs from that which exists in normal renal function. Nevertheless, the extent of CVD cannot be fully explained by these conventional risk factors, and non-conventional factors specific to CKD are now recognised to contribute to the burden of CVD. Oxidative stress is a state characterised by excessive production of reactive oxygen species (ROS) and other radical species, a reduction in the capacity of antioxidant systems, and disturbance in normal redox homeostasis with depletion of protective vascular signalling molecules such as nitric oxide (NO). This results in oxidative damage to macromolecules such as lipids, proteins and DNA which can alter their functionality. Moreover, many enzymes are sensitive to redox regulation such that oxidative modification to cysteine thiol groups results in activation of signalling cascades which result in adverse cardiovascular effects such as vascular and endothelial dysfunction. Endothelial dysfunction and oxidative stress are present in association with many conventional cardiovascular risk factors, and can be observed even prior to the development of overt, clinical, vascular pathology, suggesting that these phenomena represent the earliest stages of CVD. In the presence of CKD, there is increased ROS production due to upregulated NADPH oxidase (NOX), increase in a circulating asymmetric dimethylarginine (ADMA), uncoupling of endothelial nitric oxide synthase (eNOS) as well as other mechanisms. There is also depletion in exogenous antioxidants such as ascorbic acid and tocopherol, and a reduction in activity of endogenous antioxidant systems regulated by the master gene regulator Nrf-2. In previous studies, circulating markers of oxidative stress have been shown to be increased in CKD, together with a reduction in endothelial function in a stepwise fashion relating to the severity of renal impairment. Not only is CVD linked to oxidative stress, but the progression of CKD itself is also in part dependent on redox sensitive mechanisms. For example, administration of the ROS scavenger tempol attenuates renal injury and reduces renal fibrosis seen on biopsy in a mouse model of CKD, whilst conversely, supplementation with the NOS inhibitor L-NAME causes proteinuria and renal impairment. Previous human studies examining the effect of antioxidant administration on vascular and renal function have been conflicting however. The work contained in this thesis therefore examines the effect of antioxidant administration on vascular and endothelial function in CKD. Firstly, 30 patients with CKD stages 3 – 5, and 20 matched hypertensive controls were recruited. Participants with CKD had lower ascorbic acid, higher TAP and ADMA, together with higher augmentation index and pulse wave velocity. There was no difference in baseline flow mediated dilatation (FMD) between groups. Intravenous ascorbic acid increased TAP and O2-, and reduced central BP and augmentation index in both groups, and lowered ADMA in the CKD group only. No effect on FMD was observed. The effects of ascorbic acid on kidney function was then investigated, however this was hindered by the inherent drawbacks of existing methods of non-invasively measuring kidney function. Arterial spin labelling MRI is an emerging imaging technique which allows measurement of renal perfusion without administration of an exogenous contrast agent. The technique relies upon application of an inversion pulse to blood within the vasculature proximal to the kidneys, which magnetically labels protons allowing measurement upon transit to the kidney. At the outset of this project local experience using ASL MRI was limited and there ensued a prolonged pre-clinical phase of testing with the aim of optimising imaging strategy. A study was then designed to investigate the repeatability of ASL MRI in a group of 12 healthy volunteers with normal renal function. The measured T1 longitudinal relaxation times and ASL MRI perfusion values were in keeping with those found in the literature; T1 time was 1376 ms in the cortex and 1491 ms in the whole kidney ROI, whilst perfusion was 321 mL/min/100g in the cortex, and 228 mL/min/100g in the whole kidney ROI. There was good reproducibility demonstrated on Bland Altman analysis, with a CVws was 9.2% for cortical perfusion and 7.1% for whole kidney perfusion. Subsequently, in a study of 17 patients with CKD and 24 healthy volunteers, the effects of ascorbic acid on renal perfusion was investigated. Although no change in renal perfusion was found following ascorbic acid, it was found that ASL MRI demonstrated significant differences between those with normal renal function and participants with CKD stages 3 – 5, with increased cortical and whole kidney T1, and reduced cortical and whole kidney perfusion. Interestingly, absolute perfusion showed a weak but significant correlation with progression of kidney disease over the preceding year. Ascorbic acid was therefore shown to have a significant effect on vascular biology both in CKD and in those with normal renal function, and to reduce ADMA only in patients with CKD. ASL MRI has shown promise as a non-invasive investigation of renal function and as a biomarker to identify individuals at high risk of progressive renal impairment.

Review: Head and neck squamous cell carcinoma in sub-Saharan Africa

Aim Review the literature from 1990 to 2013 to determine known anatomic sites, risk factors, treatments, and outcomes of head and neck squamous cell carcinoma (HNSCC) in sub-Saharan Africa. Methods Using a systematic search strategy, literature pertaining to HNSCC in sub-Saharan Africa was reviewed and patient demographics, anatomic sites, histology, stage, treatment, and outcomes were abstracted. The contributions of human immunodeficiency virus (HIV), human papillomavirus (HPV) and behavioural risk factors to HNSCC in the region were assessed. Results Of the 342 papers identified, 46 were utilized for review, including 8611 patients. In sub-Saharan Africa, the oropharyngeal/oral cavity was found to be the most common site, with 7750 cases (90% of all cases). Few papers distinguished oropharyngeal from oral cavity, making identification of possible HPV-associated oropharyngeal squamous cell carcinoma (SCC) difficult. SCC of the nasopharynx, nasal cavity, or paranasal sinuses was identified in 410 patients (4.8% of all cases). Laryngeal SCC was found in 385 patients (4.5% of all cases), and only 66 patients (0.8% of all cases) with hypopharyngeal SCC were identified. In 862 patients with data available, 43% used tobacco and 42% used alcohol, and reported use varied widely and was more common in laryngeal SCC than that of the oropharyngeal/oral cavity. Toombak and kola nut use was reported to be higher in patients with HNSCC. Several papers reported HIV-positive patients with HNSCC, but it was not possible to determine HNSCC prevalence in HIV-positive compared to negative patients. Reports of treatment and outcomes were rare. Conclusions The oropharyngeal/oral cavity was by far the most commonly reported site of HNSCC reported in sub-Saharan Africa. The roles of risk factors in HNSCC incidence in sub-Saharan Africa were difficult to delineate from the available studies, but a majority of patients did not use tobacco and alcohol.

University student gambling consumption

Mestrado em Marketing

Leishmanicidal and cytotoxic activity of extracts and saponins from Ilex laurina (Aquifoliaceae)

Purpose: To evaluate the leishmanicidal and cytotoxic activity of alcohol and non-alcohol extracts and saponins from Ilex laurina . Methods: Extracts were obtained by percolation with solvents of different polarities: hexane, dichloromethane, ethyl acetate and ethanol. The ethyl acetate extract was subjected to silica gel column chromatography eluting with a step gradient of dichloromethane-methanol. All products were evaluated in vitro for leishmanicidal activity against amastigotes of leishmania panamensis and cytotoxicity on U- 937 cells. Results: Two saponins were isolated from the ethyl acetate extract. The ethyl acetate extract showed high leishmanicidal activity against intracellular amastigotes of L. panamensis (EC50, 7.5 ± 1.5 μg/mL) and low activity against axenic amastigotes (EC50, 52.8 ±1.6 μg/mL); this extract showed also high cytotoxicity (LC50, 57.7 ± 12.1 μg/mL). Saponin 2 exhibited high activity against intracellular amastigotes (EC50, 5.9 ± 0.5 μg/mL) but also showed high cytotoxicity on U-937 cells (EC50, 25.7 ± 6.1 μg/mL). This compound showed similar leishmanicidal activity and cytotoxicity to meglumine antimoniate and amphotericin B, respectively, drugs currently used for the treatment of leishmaniasis. Conclusions: Based on these results, Ilex laurina is a potential source of compounds that can lead to the development of new therapeutic alternatives against leishmaniasis.

Characterization of polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 and relationship to the alcoholism in a Colombian population

Objective: Identify and characterize polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 in a Colombian population residing in the city of Bogotá and determine its possible relationship to the alcoholism. Methods: ADH2, ADH3, ALDH2, and CYP2E1 genotypes a population of 148 individuals with non-problematic alcohol and 65 individuals with alcoholism were determined with TaqMan probes and PCR-RFLP. DNA was obtained from peripheral blood white cells. Results: Significant difference was found in family history of alcoholism and use of other psychoactive substances to compare alcoholics with controls. When allelic frequencies for each category (gender) were considered, frequency of A2 allele carriers in ADH2 was found higher in male patients than controls. In women, the relative frequency for c1 allele in CYP2E1 was lower in controls than alcoholics. The ALDH2 locus is monomorphic. No significant differences in allele distributions of the loci examined to compare two populations were observed, however when stratifying the same trend was found that these differences tended to be significant. Conclusions: This study allows us to conclude the positive association between family history of alcoholism and alcoholism suggesting that there is a favorable hereditary predisposition. Since substance dependence requires interaction of multiple genes, the combination of genotypes ADH2*2, CYP2E1*1 combined with genotype homozygous ALDH2*1 found in this study could be leading to the population to a potential risk to alcoholism.

Characterization of polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 and relationship to the alcoholism in a Colombian population

Objective: Identify and characterize polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 in a Colombian population residing in the city of Bogotá and determine its possible relationship to the alcoholism. Methods: ADH2, ADH3, ALDH2, and CYP2E1 genotypes a population of 148 individuals with non-problematic alcohol and 65 individuals with alcoholism were determined with TaqMan probes and PCR-RFLP. DNA was obtained from peripheral blood white cells. Results: Significant difference was found in family history of alcoholism and use of other psychoactive substances to compare alcoholics with controls. When allelic frequencies for each category (gender) were considered, frequency of A2 allele carriers in ADH2 was found higher in male patients than controls. In women, the relative frequency for c1 allele in CYP2E1 was lower in controls than alcoholics. The ALDH2 locus is monomorphic. No significant differences in allele distributions of the loci examined to compare two populations were observed, however when stratifying the same trend was found that these differences tended to be significant. Conclusions: This study allows us to conclude the positive association between family history of alcoholism and alcoholism suggesting that there is a favourable hereditary predisposition. Since substance dependence requires interaction of multiple genes, the combination of genotypes ADH2*2, CYP2E1*1 combined with genotype homozygous ALDH2*1 found in this study could be leading to the population to a potential risk to alcoholism.